The first product of the oxidation of purin is hypoxanthine, long recognised as a constituent of meat extracts. Adenine, the amino derivative of hypoxanthine, is met with in combination with other substances in nuclear material. The second oxidation product of purin is xanthine, and its amino derivative guanine, both of which are found in the same substances as hypoxanthine and adenine. Further oxidation of purin gives rise to uric acid. We have to recognise, also, that in addition to the purins of animal origin there are some also derived from vegetables, viz., the methyl purins, caffeine, theobromine, and theine.
Now, as will be seen later, certain compounds, containing nitrogen and phosphorus, constitute the chief, if not the exclusive, source of uric acid. These substances, long known as nucleins or nucleo-proteins, exist in the animal tissues, and in special abundance in those largely made up of cell nuclei, viz., thymus, lymph-glands, etc. The important and, indeed, the distinguishing component of the nucleins or nucleo-proteins is nucleic acid. This, in that through the action of ferments, it is from the nucleic acids that uric acid and the purin bases are derived.
But, apart from this, we have to recollect that nucleic acids yield constituents other than purin bases, viz., the pyrimidine bases, phosphoric acid, and a carbohydrate group. From a study of the structural formulæ of the pyrimidine bases it will be seen that they are closely related to the purin bases, lacking, however, one of the urea radicles. Moreover, it is believed that, though included in the makeup of nucleic acid, they are not derived from purin but are primary products.
To sum up, the characteristic constituents of nucleic acid are the purin bases (adenine, guanine, hypoxanthine, and xanthine), pyrimidine bases (uracil, cytosine, thymine), phosphoric acid and a carbohydrate group.
We have now discussed the chemical structure of uric acid and its relationship to the purin bases; but before proceeding to consider the various sources from which uric acid is derived, it will I think be convenient to consider (1) the physical properties of uric acid and (2) the condition in which it circulates in the blood.
Properties of Uric Acid
When pure, uric acid is white in colour and crystallises in rhombic form. In contrast to urea it is very insoluble, but much less so in blood serum than in distilled water, viz., ⅟₄₀₀₀₀ of water as opposed to ⅟₁₀₀₀ parts of plasma. It yields with alkalies two series of salts, viz., the biurate or mono-basic, and the so-called neutral or bi-basic urate, the latter of which is much more soluble. In water the mono-basic urate forms a colloidal solution from which the crystalline salt gradually precipitates.
The greater solubility of uric acid in blood plasma was, by Garrod and Haig, attributed to the alkalinity of the plasma. But it must be recalled that the earlier workers in this sphere judged of the alkalinity of the plasma by its reaction to litmus, a crude procedure as compared with the use of phenol-phthalein, and Frankel’s electro-potential measurements. Working with these as criteria, it has been shown that blood is normally alkaline in only a minority of cases, and indeed, according to Flack and Hill, the plasma is in reality neutral.
In the urine uric acid and the urates are held in solution by the neutral phosphates. This because the decomposition of the urates into uric acid by the acid salts of the urine is inhibited by the di-sodium phosphate present therein. Its maintenance in solution is possibly also reinforced through the influence of other constituents in the urine, notably, the urinary pigments and sodium chloride.